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Published on: June 29, 2011
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Nucleosome dynamics render heterochromatin accessible in living human cells
Hemant K Prajapati1, Zhuwei Xu1, Peter R Eriksson1
1Division of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892, USA.
Biorxiv : the Preprint Server for Biology
|January 13, 2025
Summary
Living human cells show globally accessible genomes, challenging the idea that chromatin structure blocks gene regulation. Nucleosomes in most chromatin types are dynamic, except for static centromeric regions.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Eukaryotic genomes are packaged into chromatin, influencing gene accessibility.
- Chromatin exists as euchromatin (active) and heterochromatin (repressed).
- Chromatin structure is thought to restrict transcription factor access to DNA.
Purpose of the Study:
- To measure genome accessibility in living human cells.
- To investigate the dynamic nature of chromatin in different genomic regions.
- To assess the role of chromatin accessibility in gene regulation.
Main Methods:
- Utilized an adenovirus vector to express dam DNA adenine methyltransferase in MCF7 and MCF10A cells.
- Measured genome accessibility by assessing methylation at all GATC sites in living cells.
- Compared accessibility across euchromatin, heterochromatin, and centromeric regions.
Main Results:
- The human genome is globally accessible in living cells, contrasting with isolated nuclei.
- Active promoters showed faster methylation than gene bodies and inactive promoters.
- Heterochromatic sites were only marginally less accessible than euchromatic sites.
- Centromeric chromatin sites were slowly methylated and partly inaccessible.
Conclusions:
- Nucleosomes in euchromatin and heterochromatin are highly dynamic in living cells.
- Nucleosomes in centromeric α-satellite chromatin are static.
- Simple DNA occlusion by chromatin is unlikely to be the primary mechanism for gene regulation.
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